Rfn/Un and C3H/HeJ mice will receive leukemogenic doses of total body gamma irradiation and/or cyclophosphamide for varying recovery periods. Bone marrow will be transplanted to a long-term bone marrow culture system which supports proliferation of hematopoietic stem cells in vitro for several months. Cells generated in these cultures will be tested for biologic properties of granulocytic leukemia in vitro and in vivo. The effect of serial transplantation of marrow to several generations of lethally irradiated recipient mice, or leukemogenesis by this system will be studied to determine if age and stress of serial repopulation will alter the kinetics of generation of leukemia by Rfn/Un cultures. The Rfn/Un strain develops granulocytic leukemia after irradiation while this type of leukemia in irradiated C3H/HeJ mice is very rare. Both strains develop thymic lymphoma after irradiation. The role of stromal and hematopoietic stem cells in the Rfm/Un granulocytic leukemia is being analyzed in vitro.